Changes in expression levels of drug efflux pump genes, mexB and mexY, and porin gene oprD in Pseudomonas aeruginosa were investigated in this study. Fifty-five multidrug-resistant P. aeruginosa (MDRP) strains were compared with 26 drug-sensitive strains and 21 strains resistant to a single antibiotic. The effect of the efflux inhibitor Phe-Arg-β-naphthylamide on drug susceptibility was determined, and gene expression was quantified using real-time quantitative real-time reverse transcription polymerase chain reaction. In addition, the levels of metallo-β-lactamase (MBL) and 6′-N-aminoglycoside acetyltransferase [AAC(6′)-Iae] were investigated. Efflux pump inhibitor treatment increased the sensitivity to ciprofloxacin, aztreonam, and imipenem in 71%, 73%, and 29% of MDRPs, respectively. MBL and AAC(6′)-Iae were detected in 38 (69%) and 34 (62%) MDRP strains, respectively. Meanwhile, 76% of MDRP strains exhibited more than 8-fold higher mexY expression than the reference strain PAO1. Furthermore, 69% of MDRP strains expressed oprD at levels less than 0.01-fold of those in PAO1. These findings indicated that efflux pump inhibitors in combination with ciprofloxacin or aztreonam might aid in treating MDRP infections.

本研究调查了铜绿假单胞菌中药物外排泵基因mexB和mexY以及孔蛋白基因oprD表达水平的变化。将 55 种多重耐药铜绿假单胞菌(MDRP) 菌株与 26 种药物敏感菌株和 21 种对单一抗生素耐药的菌株进行了比较。确定外排抑制剂 Phe-Arg-β-萘酰胺对药物敏感性的影响，并使用实时定量逆转录聚合酶链反应对基因表达进行定量。此外，还研究了金属-β-内酰胺酶 (MBL) 和 6'-N-氨基糖苷乙酰转移酶 [AAC(6')-Iae] 的水平。外排泵抑制剂治疗分别增加了 71%、73% 和 29% 的 MDRP 对环丙沙星、氨曲南和亚胺培南的敏感性。分别在 38 个 (69%) 和 34 个 (62%) MDRP 菌株中检测到 MBL 和 AAC(6')-Iae。同时，76% 的 MDRP 菌株的mexY表达量比参考菌株 PAO1高 8 倍以上。此外，69% 的 MDRP 菌株表达oprD的水平低于 PAO1 的 0.01 倍。这些发现表明，外排泵抑制剂与环丙沙星或氨曲南联合可能有助于治疗 MDRP 感染。